Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk

Anurag Mehta, Nestor Vasquez, Colby R. Ayers, Jaideep Patel, Ananya Hooda, Amit Khera, Roger S. Blumenthal, Michael D. Shapiro, Carlos J. Rodriguez, Michael Y. Tsai, Laurence S. Sperling, Salim S. Virani, Michael J. Blaha, Parag H. Joshi

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Background: Elevated lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in combination. Objectives: This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk. Methods: Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor–adjusted Cox regression models. Results: Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS. Conclusions: Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions.

Original languageEnglish (US)
Pages (from-to)757-768
Number of pages12
JournalJournal of the American College of Cardiology
Issue number8
StatePublished - Mar 1 2022

Bibliographical note

Funding Information:
The authors thank the other investigators, the staff, and the participants of the MESA and DHS studies for their valuable contributions. A full list of participating MESA study investigators and institutions can be found at online.

Publisher Copyright:
© 2022 American College of Cardiology Foundation


  • atherosclerotic cardiovascular disease
  • coronary artery calcium
  • lipoprotein(a)
  • primary cardiovascular disease prevention

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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